Reversal of Ketamine Pharmacodynamic Effects With Naloxone

Ullevaal University Hospital

Status and phase: Terminated; Phase 4

Conditions: Pain

Treatments: Drug: Saline; Drug: Saline + Ketamine; Drug: Naloxone + Ketamine; Drug: Naloxone + Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00921765

DOK-018

Details and patient eligibility

About

The purpose of this study is to determine whether the analgetic and other effects effect of ketamine are partly mediated through opioid receptors

Full description

Ketamine er et dissociative anaesthetic closely related with phencyclidine (PCP). Phencyclidine is a non-competitive NMDA-antagonist, and it is assumed that the pharmacodynamic mechanism of action for ketamine is the same. Receptor binding studies shows that ketamine has affinity to many receptor types, including opioid mu and kappa receptors. Ketamine has only about 25 times lower affinity for kappa receptors than for the NMDA-receptor complex. Naloxone is a specific antagonist for opioid receptors and block both mu og kappa receptors. A dose of naloxone 10 times larger than required to block mu receptors is required to block kappa receptors. Experiments with naloxone suggest that ketamine is not a mu agonist, but experiments with sufficient large naloxone doses to block kappa receptors have not been carried out in humans.

Enrollment: 3 patients

Sex: Female

Ages: 18 to 30 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Females of norwegian Caucasian origin who needs surgical removal of impacted third molars

Exclusion criteria

• Anamnestic information regarding psychiatric diagnosis regarding mother/father or brother/sister Concommitant medication other than oral contraceptives Hypersensitivity towards NSAID/opioids/study drugs Females with suspected or confirmed pregnancy Lactating females Surgery lasting more than 60 minutes

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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3 participants in 4 patient groups, including a placebo group

Placebo + Placebo

Placebo Comparator group

Description:

Saline single bolus dose iv + saline single bolus dose iv

Treatment:

Drug: Saline

Placebo + Ketamine

Active Comparator group

Description:

Saline single bolus dose followed by single bolus dose of ketamine 0.2 mg/kg bw

Treatment:

Drug: Saline + Ketamine

Naloxone + Placebo

Active Comparator group

Description:

Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline

Treatment:

Drug: Naloxone + Placebo

Naloxone + Ketamine

Active Comparator group

Description:

Single bolus dose of ketamine 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw

Treatment:

Drug: Naloxone + Ketamine